Butenafine

Butenafine
Clinical data
Trade names	Mentax, Lotrimin Ultra
AHFS/Drugs.com	Monograph
Routes of; administration	Topical (cream)
ATC code	D01AE23 (WHO) ;
Legal status
Legal status	OTC (Lotrimin Ultra), Rx-only (Mentax);
Pharmacokinetic data
Metabolism	Hepatic
Elimination half-life	35–100 hours
Identifiers
	IUPAC name [(4-tert-butylphenyl)methyl](methyl)(naphthalen-1-ylmethyl)amine;
CAS Number	101828-21-1 ;
PubChem CID	2484;
DrugBank	DB01091 ;
ChemSpider	2390 ;
UNII	91Y494NL0X;
KEGG	D07596 ;
ChEBI	CHEBI:3238 ;
ChEMBL	ChEMBL990 ;
CompTox Dashboard (EPA)	DTXSID7040657 ;
Chemical and physical data
Formula	C23H27N
Molar mass	317.476 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES N(C)(Cc1ccc(cc1)C(C)(C)C)Cc3c2ccccc2ccc3;
	InChI InChI=1S/C23H27N/c1-23(2,3)21-14-12-18(13-15-21)16-24(4)17-20-10-7-9-19-8-5-6-11-22(19)20/h5-15H,16-17H2,1-4H3 ; Key:ABJKWBDEJIDSJZ-UHFFFAOYSA-N ;
	(verify)

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Butenafine, sold under the brand names Lotrimin Ultra, Mentax, and Butop (In India only), is a synthetic benzylamine derived antifungal drug.

It is structurally related to the allylamine antifungals terbinafine & naftifine.

Medical uses

Butenafine is indicated for the topical treatment of tinea (pityriasis) versicolor due to Malassezia furfur, as well as athlete's foot (Tinea pedis), ringworm (Tinea corporis) and jock itch (Tinea cruris) due to Epidermophyton floccosum, Trichophyton mentagrophytes, Trichophyton rubrum, and Trichophyton tonsurans.

It also displays superior activity against Candida albicans than terbinafine and naftifine. Butenafine demonstrates low minimum inhibitory concentrations against Cryptococcus and Aspergillus.

There is some evidence that it is effective against dermatophyte infections of the toenails, but needs to be applied daily for prolonged periods (at least one year).^[2]

Available forms

Butenafine is typically available as a 1% topical cream.

Pharmacology

Like the allylamine antifungals (e.g terbinafine), butenafine works by inhibiting the synthesis of ergosterol by binding to and inhibiting squalene epoxidase, an enzyme in the pathway used for creation of the sterols needed in fungal cell membranes. Lacking ergosterol, the cell membranes increase in permeability, allowing their contents to leak out. Furthermore, inhibition of squalene epoxidase leads to a toxic buildup of squalene. This double action of butenafine (increased membrane permeability and toxic buildup of squalene) makes butenafine fungicidal rather than merely fungistatic.

In addition to being an antifungal, butenafine is an anti inflammatory. Because fungal skin infections are often accompanied by significant inflammation, this is a desirable property. The fact that butenafine has intrinsic anti inflammatory properties is also desirable since it is not necessary to add topical glucocorticoids, which often come with undesired side effects.

Chemistry

Butenafine hydrochloride is an odorless white crystalline powder that is freely soluble in methanol, ethanol, and chloroform, yet is only slightly soluble in water.

Synthesis

Reductive amination of 1-naphthaldehyde (1) with methylamine (2) gives the intermediate secondary amine (3). Alkylation of this with p-tert-butyl benzyl bromide (4) yields the tertiary amine butenafine.^[3]^[4]^[5]

References

^ Mylan Pharmaceuticals Inc. "Mentax (butenafine hydrochloride) Cream. Human Prescription Drug Label". dailymed.nlm.nih.gov. National Institutes of Health, U.S. National Library of Medicine, Health & Human Services. Retrieved 24 August 2016.
^ Crawford F, Hollis S (July 2007). "Topical treatments for fungal infections of the skin and nails of the foot". The Cochrane Database of Systematic Reviews. 2007 (3): CD001434. doi:10.1002/14651858.CD001434.pub2. PMC 7073424. PMID 17636672.
^ US patent 5021458, Maeda T, Yamamoto T, Takase M, Sasaki K, Arika T, Yokoo M, Hashimoto R, Amemiya K, Koshikawa S, "Amine derivatives and fungicides containing the same", issued 1991-06-04, assigned to Kaken Pharmaceutical Co Ltd
^ Maeda T, Takase M, Ishibashi A, Yamamoto T, Sasaki K, Arika T, et al. (February 1991). "[Synthesis and antifungal activity of butenafine hydrochloride (KP-363), a new benzylamine antifungal agent]". Yakugaku Zasshi (in Japanese). 111 (2): 126–137. doi:10.1248/yakushi1947.111.2_126. PMID 2056447.
^ "Butenafine". Pharmaceutical Substances. Thieme. Retrieved 2024-07-04.

[1] Mylan Pharmaceuticals Inc. "Mentax (butenafine hydrochloride) Cream. Human Prescription Drug Label". dailymed.nlm.nih.gov. National Institutes of Health, U.S. National Library of Medicine, Health & Human Services. Retrieved 24 August 2016.

[2] Crawford F, Hollis S (July 2007). "Topical treatments for fungal infections of the skin and nails of the foot". The Cochrane Database of Systematic Reviews. 2007 (3): CD001434. doi:10.1002/14651858.CD001434.pub2. PMC 7073424. PMID 17636672.

[3] US patent 5021458, Maeda T, Yamamoto T, Takase M, Sasaki K, Arika T, Yokoo M, Hashimoto R, Amemiya K, Koshikawa S, "Amine derivatives and fungicides containing the same", issued 1991-06-04, assigned to Kaken Pharmaceutical Co Ltd

[4] Maeda T, Takase M, Ishibashi A, Yamamoto T, Sasaki K, Arika T, et al. (February 1991). "[Synthesis and antifungal activity of butenafine hydrochloride (KP-363), a new benzylamine antifungal agent]". Yakugaku Zasshi (in Japanese). 111 (2): 126–137. doi:10.1248/yakushi1947.111.2_126. PMID 2056447.

[5] "Butenafine". Pharmaceutical Substances. Thieme. Retrieved 2024-07-04.

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